Recent studies suggest that a primary factor in the early and preferential growth of preneoplastic cells in the liver is a relative resistance to the toxic effects of the chemical carcinogen. Liver necrosis provides the growth stimulus, and the relative resistance of initiated cells establishes the growth advantage. Such a view would imply that prevention of the necrosis induced by liver carcinogens whould prevent the appearance of cancer in spite of the continued presence of the carcinogen and the existence of initiated cells. To attempt to achieve such prevention necessitates a more detailed knowledge of the mechanisms underlying the toxic cell death produced by liver carcinogens. Studies to provide such information are proposed that are based on the work carried out in the previous grant period. Emphasis will be placed on the role of an influx of calcium ions on the inhibition of such fluxes and the effects of such inhibition on liver cell necrosis and carcinogenesis produced in the rat by carbon tetrachloride, dimethylnitrosamine and aflatoxin B(1).